The prostate gland is a chestnut-shaped, hard mass of tissue located in the anteroinferior part of the male urinary bladder and between the urinary bladder and the urogenital diaphragm. The average weight of the adult prostate gland is about 20 grams. The urethra and a pair of ejaculatory ducts run through the center front of the prostate gland, thereby the prostate gland is anatomically divided into four lobes, When a man ages over 50, production of testosterone decreases and atrophic changes occur to the prostate gland, which performs secretory functions during a man's youth and middle age, and the functions thereof are decreased. From this time onwards, fibromuscular or glandular nodules appear on the glands around the urethra and gradually grow into large nodes. These nodes are benign tumors. The prostate gland with these nodes enlarges as a whole (60 to 100 g), this being called benign prostatic hyperplasia. The incidence of histologically enlarged prostate (enlarged nodes) increases with age. Prostatic hyperplasia is recognized in 50% of males over 60 years old, and about 90% of those over 85 years old.
Although the definition of benign prostatic hyperplasia (BPH) is not absolutely clear, it is understood as a disease that causes obstruction of the urethra due to the enlarged prostate gland. The subjective symptoms of benign prostatic hyperplasia are roughly divided into two types, i.e., obstructive symptoms such as urination difficulty, anuresis, prolonged urination, intermittent urination, and the like; and irritable symptoms such as frequent urination, urinary incontinence, nocturia, urinary urgency, and the like. The aforementioned obstructive symptoms is considered to be caused by two different mechanisms, i.e., organic obstruction in which enlarged prostate tumors press the urethra, and functional obstruction in which the prostatic capsule and stromal smooth muscles contract in response to sympathetic nerve stimulation. The functional obstruction is known to be caused by the stimulation of the sympathetic nervous system through α-receptors, and the therapeutic effect of such functional obstruction has recently been increased due to the development of α-blockers. However, the specific mechanism inducing organic obstruction has not yet been revealed, and no effective therapeutic agents have been developed. Therefore, the immediate development of such therapeutic agents is desired.
The prostate tissue primarily consists of epithelial and stromal components. In human benign prostatic hyperplasia in which organic disorders are caused by the enlargement of the prostate tissue, it has been reported that stromal enlargement resulting from the increase of stromal components is frequently observed as a morphologic feature. The increase of epithelial components is known to result primarily from the growth of hormone-sensitive epithelial cells, and as a therapeutic agent anti-hormonal agents are used. However, no pharmaceuticals that can specifically inhibit the above-described stromal enlargement that is frequently observed in humans are known. Therefore, demand exists for pharmaceuticals that have activity to specifically inhibit or improve such prostatic stromal hyperplasia.
Incidentally, for developing or evaluating pharmaceuticals, it is known that using an animal model that reflects specific human pathological condition instead of using a normal animal, when screening medicinal ingredients or evaluating pharmacological actions of various substances provides results closer to actual clinical data.